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1.
Can J Ophthalmol ; 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38159912

RESUMO

OBJECTIVE: To describe pediatric patients with CACNA1F-associated incomplete X-linked congenital stationary night blindness presenting without nyctalopia, and review the causes leading to diagnosis delay. DESIGN: Retrospective cohort. METHODS: This was set in a single institution between 2004 and 2019. There were12 patients. The intervention or observation procedures used were clinical course, visual acuity, refractive error, images, electrophysiology, genetic testing, pedigree. The main outcome measures were cohort description and causes of diagnosis delay. RESULTS: For these 12 cases, the referring diagnosis was congenital nystagmus (7), reduced best-corrected visual acuity (BCVA, 4), and progressive myopia (1). Nyctalopia was not a presenting symptom and developed in 4 patients during follow-up. Seven patients presented with nystagmus. All patients developed early-onset myopia. Myopia progressed more rapidly before age 6 than after (average 1.14 D vs 0.25 D) (p = 0.0033). The average final BCVA was 20/50 (20/30-20/150). Vision at presentation was correlated with final visual acuity (r2 = 0.87, p = 5.4E-06). The first cycloplegic refraction was correlated to the final refractive error (r2 = 0.49, p = 0.009). Patients with nystagmus had worse BCVA on average. Full-field electroretinogram was abnormal and diagnostic in all cases, as confirmed by genetic testing. The average time to diagnosis was 4.2 years, and the average age at diagnosis was 7.9 years. The delay in diagnosis was due to the absence of nyctalopia, not performing an electroretinogram and/or an alternative diagnosis. CONCLUSIONS: In children, CACNA1F-associated synaptic dysfunction does not usually present with night blindness. It should be suspected in male patients with early-onset myopia, especially with a history of nystagmus.

2.
Nat Med ; 28(5): 1014-1021, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35379979

RESUMO

CEP290-associated Leber congenital amaurosis type 10 (LCA10) is a retinal disease resulting in childhood blindness. Sepofarsen is an RNA antisense oligonucleotide targeting the c.2991+1655A>G variant in the CEP290 gene to treat LCA10. In this open-label, phase 1b/2 ( NCT03140969 ), 12-month, multicenter, multiple-dose, dose-escalation trial, six adult patients and five pediatric patients received ≤4 doses of intravitreal sepofarsen into the worse-seeing eye. The primary objective was to evaluate sepofarsen safety and tolerability via the frequency and severity of ocular adverse events (AEs); secondary objectives were to evaluate pharmacokinetics and efficacy via changes in functional outcomes. Six patients received sepofarsen 160 µg/80 µg, and five patients received sepofarsen 320 µg/160 µg. Ten of 11 (90.9%) patients developed ocular AEs in the treated eye (5/6 with 160 µg/80 µg; 5/5 with 320 µg/160 µg) versus one of 11 (9.1%) in the untreated eye; most were mild in severity and dose dependent. Eight patients developed cataracts, of which six (75.0%) were categorized as serious (2/3 with 160 µg/80 µg; 4/5 with 320 µg/160 µg), as lens replacement was required. As the 160-µg/80-µg group showed a better benefit-risk profile, higher doses were discontinued or not initiated. Statistically significant improvements in visual acuity and retinal sensitivity were reported (post hoc analysis). The manageable safety profile and improvements reported in this trial support the continuation of sepofarsen development.


Assuntos
Amaurose Congênita de Leber , Adulto , Antígenos de Neoplasias/genética , Cegueira/genética , Proteínas de Ciclo Celular/genética , Criança , Proteínas do Citoesqueleto/metabolismo , Humanos , Amaurose Congênita de Leber/tratamento farmacológico , Amaurose Congênita de Leber/genética , Oligonucleotídeos Antissenso/efeitos adversos , Visão Ocular
3.
J AAPOS ; 25(4): 220.e1-220.e8, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34280564

RESUMO

PURPOSE: To present a series of patients diagnosed with oculocutaneous albinism (OCA) based on clinical presentation who were later proven to have a different diagnosis. METHODS: The medical records of patients seen at the Pediatric Inherited Eye Disease Clinic of the University of Iowa from 1980 to 2018 who were eventually discovered to have an incorrect diagnosis of OCA were reviewed retrospectively. RESULTS: Eight pediatric patients presenting with clinical features suggestive of OCA which changed to a different diagnosis over time were identified. Presenting clinical features included fair pigmentation of the skin and adnexa (8/8), congenital nystagmus (6/8), decreased visual acuity (8/8), iris transillumination defects (8/8), and foveal hypoplasia (7/8). Of the 8 patients, 4 manifested progressive, preschool-age-onset myopia. Other associated clinical features included hearing loss (3), seizures (1), abnormal chest x-ray (1) and easy bruising (2). During follow-up, additional clinical features and genetic testing proved that they have different clinical entities, namely, Knobloch syndrome, Jeune syndrome, Donnai-Barrow syndrome, Waardenburg syndrome, Aniridia syndrome, Stickler syndrome, and Hermansky-Pudlak syndrome, one of the syndromic types of OCA. CONCLUSIONS: Clinical features used to diagnose OCA also occur in other disorders. For a definitive diagnosis of OCA, ancillary/genetic testing must be performed. Clinical features not typically found in association with albinism, such as hearing loss, or early onset, or progressive myopia, may indicate the need for more extensive investigation.


Assuntos
Albinismo Oculocutâneo , Albinismo , Síndrome de Hermanski-Pudlak , Nistagmo Congênito , Albinismo Oculocutâneo/genética , Criança , Pré-Escolar , Humanos , Fenótipo , Estudos Retrospectivos
4.
Ophthalmic Genet ; 41(2): 151-158, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32281467

RESUMO

Background: Usher syndrome is the most common hereditary syndrome combining deafness and blindness. In the 2017 National Child Count of Children and Youth who are Deaf-Blind, Usher syndrome represented 329 of 10,000 children, but there were also at least 70 other etiologies of deaf-blindness documented. The purpose of this study was to analyze the work-up and ultimate diagnoses of 21 consecutive families who presented to the Genetic Eye-Ear Clinic (GEEC) at the University of Iowa. Our hypothesis was that most families referred to the GEEC would have initial and final diagnoses of Usher syndrome.Materials and Methods: Patients were identified through an IRB approved retrospective chart review of referrals to the GEEC between 2012 and 2019. Details about each patient's history, exam, and clinical and genetic work-up were recorded.Results: From 2012 to 2019, 21 families (25 patients) were referred to the collaborative GEEC. Overall molecular diagnostic rate in this cohort was 14/21 (67%). Evaluation resulted in a change of diagnosis in 11/21 (52%) families. Ultimately, there were eleven unique diagnoses including hereditary, non-hereditary, and independent causes of combined visual impairment and hearing loss. The most common diagnosis was Usher syndrome, which represented 6/21 (29%) families.Conclusions: Providing a correct diagnosis for patients with visual impairment and hearing loss can be challenging for clinicians and their patients, but it can greatly improve clinical care and outcomes. We recommend an algorithm that includes multidisciplinary collaboration, careful clinical evaluation, strategic molecular testing, and consideration of a broad differential diagnosis.


Assuntos
Cegueira/diagnóstico , Surdez/diagnóstico , Marcadores Genéticos , Mutação , Síndromes de Usher/diagnóstico , Adolescente , Adulto , Cegueira/genética , Criança , Pré-Escolar , Surdez/genética , Diagnóstico Diferencial , Feminino , Seguimentos , Predisposição Genética para Doença , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Síndromes de Usher/genética
5.
Nat Med ; 25(2): 225-228, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30559420

RESUMO

Photoreceptor ciliopathies constitute the most common molecular mechanism of the childhood blindness Leber congenital amaurosis. Ten patients with Leber congenital amaurosis carrying the c.2991+1655A>G allele in the ciliopathy gene centrosomal protein 290 (CEP290) were treated (ClinicalTrials.gov no. NCT03140969 ) with intravitreal injections of an antisense oligonucleotide to restore correct splicing. There were no serious adverse events, and vision improved at 3 months. The visual acuity of one exceptional responder improved from light perception to 20/400.


Assuntos
Cílios/patologia , Amaurose Congênita de Leber/tratamento farmacológico , Amaurose Congênita de Leber/fisiopatologia , Oligonucleotídeos Antissenso/administração & dosagem , Oligonucleotídeos Antissenso/uso terapêutico , Células Fotorreceptoras de Vertebrados/patologia , Visão Ocular , Adulto , Alelos , Antígenos de Neoplasias/genética , Proteínas de Ciclo Celular , Cílios/efeitos dos fármacos , Proteínas do Citoesqueleto , Feminino , Humanos , Injeções Intravítreas , Masculino , Proteínas de Neoplasias/genética , Adulto Jovem
6.
Am J Ophthalmol ; 190: 58-68, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29559409

RESUMO

PURPOSE: GUCY2D has been associated with autosomal recessive Leber congenital amaurosis and autosomal dominant cone-rod dystrophy. This report expands the phenotype of autosomal recessive mutations to congenital night blindness, which may slowly progress to mild retinitis pigmentosa. DESIGN: Retrospective case series. METHODS: Multicenter study of 5 patients (3 male, 2 female). RESULTS: All patients presented with night blindness since childhood. Age at referral was 9-45 years. Length of follow-up was 1-7 years. Best-corrected visual acuity at presentation ranged from 20/15 to 20/30 and at most recent visit averaged 20/25. No patient had nystagmus or high refractive error. ISCEV standard electroretinography revealed nondetectable dark-adapted dim flash responses and reduced amplitude but not electronegative dark-adapted bright flash responses with similar waveforms to the reduced-amplitude light-adapted single flash responses. The 30 Hz flicker responses were relatively preserved. Macular optical coherence tomography revealed normal lamination in 3 patients, with abnormalities in 2. Goldmann visual fields were normal at presentation in children but constricted in 1 adult. One child showed loss of midperipheral fields over time. Fundus appearance was normal in childhood; the adult had sparse bone spicule-like pigmentation. Full-field stimulus testing (FST) revealed markedly decreased retinal sensitivity to light. Dark adaptation demonstrated lack of rod-cone break. Two patients had tritanopia. All 5 had compound heterozygous mutations in GUCY2D. Three of the 5 patients harbor the Arg768Trp mutation reported in GUCY2D-associated Leber congenital amaurosis. CONCLUSIONS: Autosomal recessive GUCY2D mutations may cause congenital night blindness with normal acuity and refraction, and unique electroretinography. Progression to mild retinitis pigmentosa may occur.


Assuntos
Oftalmopatias Hereditárias/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Guanilato Ciclase/genética , Mutação , Miopia/genética , Cegueira Noturna/genética , Receptores de Superfície Celular/genética , Retinose Pigmentar/genética , Adolescente , Criança , Distrofias de Cones e Bastonetes/genética , Adaptação à Escuridão , Eletrorretinografia , Feminino , Genes Recessivos , Humanos , Amaurose Congênita de Leber/genética , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Refração Ocular/fisiologia , Estudos Retrospectivos , Acuidade Visual/fisiologia , Testes de Campo Visual , Campos Visuais/fisiologia
7.
Ophthalmic Genet ; 36(4): 359-64, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24547931

RESUMO

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) presents with progressive vision loss at 4-7 years of age. Blindness results within 2 years, followed by inexorable neurologic decline and death. There is no treatment or cure. Neuroinflammation is postulated to play a role in the neurodegeneration. The JNCL mouse model demonstrated decreased neuroinflammation and improved motor skills with immunosuppression. Based on this work, a short-term human clinical trial of mycophenolate mofetil has begun, however longer term effects, and whether immunosuppression modulates vision loss, have not been studied. We report a JNCL patient treated with immunosuppressive therapy in whom visual function was comprehensively characterized over 2 years.


Assuntos
Imunossupressores/uso terapêutico , Ácido Micofenólico/análogos & derivados , Lipofuscinoses Ceroides Neuronais/tratamento farmacológico , Degeneração Retiniana/tratamento farmacológico , Criança , Análise Mutacional de DNA , Adaptação à Escuridão , Eletrorretinografia , Feminino , Humanos , Glicoproteínas de Membrana/genética , Chaperonas Moleculares/genética , Ácido Micofenólico/uso terapêutico , Lipofuscinoses Ceroides Neuronais/diagnóstico , Lipofuscinoses Ceroides Neuronais/genética , Estimulação Luminosa , Degeneração Retiniana/diagnóstico , Degeneração Retiniana/genética , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual/efeitos dos fármacos
8.
J AAPOS ; 9(2): 107-11, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15838435

RESUMO

PURPOSE: To determine the effectiveness and side effects of full-time occlusion for the treatment of amblyopia. METHODS: Patients with unilateral amblyopia secondary to strabismus, anisometropia, or a combination of the two were retrospective reviewed. All patients had full-time occlusion encompassing 24 hours per day or all waking hours, followed to a defined endpoint. Success was defined as 20/30 or better or equal visual acuity by fixation pattern between the two eyes. The ultimate goal was equal visual acuity. RESULTS: Six hundred patients fit the inclusion criteria. Mean follow-up after the cessation of full-time patching was 7.2 years. Eighty-nine percent were followed for more than 1 year. Mean age at last follow-up visit was 10.82 years. Ninety-six percent of patients attained a successful visual result. Sixty percent attained equal visual acuity. Younger patients required less occlusion time to endpoint and had a better visual outcome ( P < 0.0001). Initial visual acuity was significantly related to best visual acuity attained ( P < 0.0001). The incidence of occlusion amblyopia was 25.8%. CONCLUSIONS: Full-time occlusion produces excellent visual acuity results. It was shown to be effective with no long-term complications if patients proceed as directed.


Assuntos
Ambliopia/terapia , Privação Sensorial , Acuidade Visual/fisiologia , Adolescente , Adulto , Ambliopia/etiologia , Ambliopia/fisiopatologia , Anisometropia/complicações , Criança , Pré-Escolar , Seguimentos , Humanos , Lactente , Refração Ocular/fisiologia , Estudos Retrospectivos , Estrabismo/complicações , Fatores de Tempo , Resultado do Tratamento
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